1. Field of the Invention
The present invention relates to a novel resin composition wherein a resin additive itself has degradability. The resin composition of the present invention is a novel resin composition having improved wettability, and is especially useful as a degradable plastic or a bioabsorbable plastic which can be degraded under a natural environment or in a living body. Furthermore, the present invention relates to a method for accelerating the hydrolysis of a resin such as an aliphatic polyester, and a method for inhibiting its heat deterioration.
2. Description of the Related Art
Polyhydroxycarboxylic acids typified by polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL) and the like are utilized as biodegradable plastics which can be degraded by water, an enzyme and the like under a natural environment of in a living body.
Moreover, Japanese Application Laid-Open No. 64824/1987, for example, discloses a method for obtaining a lactic acid-glycolic acid copolymer (PLGA) useful as a base material for a slowly releasable agent and having a low molecular weight and a polydispersity by the ring-opening polymerization of glycolide (GLD) which is a cyclic dimer of glycolic acid and lactide (LTD) which is a cyclic dimer of lactic acid.
In recent years, as global environment is getting worse, much attention is increasingly paid to the recycling of resins and the use of additives which are safe for living bodies and less harmful to the global environment. In addition, with the diversification of consumer""s needs, demands for biodegradable plastics such as polyhydroxycarboxylic acids also increase. For example, a phthalic ester-based plasticizer which is one of resin plasticizers is considered as an endocrine disrupting substance (an environmental hormone), and thus its safety is insufficient. Accordingly, it is proposed to restrict the use of the phthalic ester-based plasticizers, and for the replacement of these plasticizers, research has been conducted for safer resin additives.
For example, PLA is utilized as a material for disposable containers, packaging materials and the like owing to its good processability and the excellent mechanical strength of its molded products. However, PLA has a disadvantage that its degradation velocity is relatively slow under conditions (e.g., in sea water, soil or the like) other than in compost, and hence PLA can scarcely be used in a field where it is desired that PLA degrades and vanishes within several months.
Accordingly, in order to accelerate the hydrolysis of PLA, mixing a hydrophilic additive such as polyethylene glycol can also be conceived. However, PLA is less hydrophilic, and for this reason, it is scarcely compatible to a hydrophilic substance such as polyethylene glycol. Therefore, the additive tends to bleed out during molding or after molding, the mechanical strength of molded articles decreases, and appearance such as transparency is impaired. In consequence, such a conception is not practical.
So far as the inventors know, there has not been found yet, for example, a method which comprises adding an additive to an aliphatic polyester such as PLA to effectively accelerate degradability without remarkably impairing the properties of the aliphatic polyester (mechanical strength, appearance and the like).
On the other hand, also in the field of the slowly releasable agents, there is highly required a product that can slowly release an agent within a relatively short period of time. With regard to PLA, its degradation in a body is too slow, so that it remains in the boy for a long time after the agent has been released, which is not preferable. Therefore, a product having a high degradation velocity has been investigated, for example, by using PLGA of a low molecular weight instead of PLA. However, PLGA still is not all-purpose, and some problems are indicated, for example, as follows.
(1) PLGA is amorphous and has a glass transition temperature (Tg) of around 30 to 40xc2x0 C., and therefore, a product containing it softens and adhesively melts in summer season.
(2) In manufacturing a product by adding a hydrophobic agent, an incorporation ratio of the agent (the content of the agent in the product) does not increase.
(3) Since PLGA is a copolymer, the scattering of quality occurs between lots in a polymer production process.
Accordingly, it would be an important contribution in the field of the slowly releasable agent to realize the acceleration of the biodegradation of a crystalline and hydrophobic homopolymer such as PLA. Namely, a method for accelerating the degradation of an aliphatic polyester is desired also in an application where it is used in a living body.
Furthermore, in the case of an aliphatic polyester such as PLA, especially a high-molecular weight polymer, it is known that the remarkable decrease of the molecular weight occurs by heating during molding. However, an effective method for inhibiting the heat deterioration of the aliphatic polyester has not been developed yet.
An objective of the present invention is to provide a novel resin composition wherein hydrolysis is accelerated and heat deterioration is inhibited.
Another objective of the present invention is to provide a method capable of blending an additive with a resin without separation and also capable of accelerating the hydrolysis of a resin such as an aliphatic polyester or inhibiting the heat deterioration of the same by the function of the additive.
As a result of intensive studies for achieving the above objectives, the present inventors have found that when a copolymer having a hydrophilic segment and a hydrophobic segment is mixed with a resin such as a polyester, they can be mixed without separation and also the wettability of the resin can be enhanced, whereby hydrolysis can be accelerated. Furthermore, they have also found that when the copolymer is mixed with a resin such as, especially, a polyhydroxycarboxylic acid, remarkable effects can be exerted. That is to say, a degradation rate can be increased and heat deterioration during heating can be inhibited without impairing the properties of the polyhydroxycarboxylic acid.
Namely, a first aspect of the present invention is directed to a resin composition comprising a block or a graft copolymer (A) having a polyamino acid as a hydrophilic segment (a-1) and a degradable polymer as a hydrophobic segment (a-2), and a resin (B).
Furthermore, a second aspect of the present invention is directed to a method for accelerating the hydrolysis of a resin which comprises the step of mixing 1 to 50% by weight of a copolymer (A) having a weight-average molecular weight of 1000 to 100000 with a resin (B) having a weight-average molecular weight of 3000 to 500000.
A third aspect of the present invention is directed to a method for inhibiting the heat deterioration of a resin.
A resin composition of the present invention comprises a block or a graft copolymer (A) and a resin (B).
Typical examples of the resin (B) for use in the present invention includes, but are not limited to, the following resins including degradable resins.
1. Polyolefin-based resins
High density polyethylene, low density polyethylene, linear low density polyethylene, polypropylene, polyisopropylene, polyisobutylene, polybutadiene, and the like; homopolymers and copolymers synthesized from one or more of olefin monomers such as ethylene, propylene and butylene; copolymers with any other monomers; and mixtures thereof.
2. Polystyrene-based resins
Polystyrene, acrylonitrile-butadiene-styrene copolymer and the like; homopolymers and copolymers synthesized from one or more of styrene-based monomers; copolymers with any other monomers; and mixtures thereof.
3. Polycarbonates
Homopolymers and copolymers synthesized from one or more of polyoxymethylene, polybutylene terephthalate, polyethylene terephthalate, polyphenylene oxide and the like; copolymers with the any other monomers; and mixtures thereof.
4. Degradable resins
4-1. Aliphatic polyesters
(1) Polyhydroxylcarboxylic acids
Homopolymers and copolymers synthesized from one or more of hydroxycarboxylic acids such as xcex1-hydroxymonocarboxylic acids (e.g., glycolic acid, lactic acid, 2-hydroxybutyric acid, 2-hydroxyvaleric acid, 2-hydroxycaproic acid and 2-hydroxycapric acid), hydroxydicarboxylic acids (e.g., malic acid), hydroxytricarboxylic acids (e.g., citric acid); copolymers with any other monomers; and mixtures thereof.
(2) Polylactides
Homopolymers and copolymers synthesized from one or more of lactides such as glycolide, lactide, benzylmalolactonate, malide benzyl ester and 3-[(benzyloxycarbonyl)methyl]-1,4-dioxan-2,5-dione; copolymers with any other monomers; and mixtures thereof.
(3) Polylactones
Homopolymers and copolymers synthesized from one or more of lactones such as xcex2-propiolactone, xcex4-valerolactone, xcex5-caprolactone and N-benzyloxycarbonyl-L-serin-xcex2-lactone; copolymers with any other monomers; and mixtures thereof. Especially, they may each copolymerize with glycollide or lactide which is a cyclic dimer of an xcex1-hydroxy acid.
4-2. Polyanhydrides
For example, poly[1,3-bis(p-carboxyphenoxy)methane] and poly(terphthalic acid-sebacic anhydride).
4-3. Degradable polycarbonates
For example, poly(oxycarbonyloxyethylene) and spiroorthopolycarbonate.
4-5. Polyorthoesfers
For example, poly(3,9-bis(ethylidene)-2,4,8,10-tetraoxaspiro [5.5] undecan-1,6-hexandiol).
4-6. Poly-xcex1-cyanoacrylic esters
For example, poly (isobutyl xcex1-cyanoacrylate).
4-7. Polyphosphazenes
For example, polydiaminophosphazene.
4-8. Other degradable resins
Synthetic resins typified by polyhydroxyesters which can be produced with the aid of microorganisms; and resins to which degradability is imparted by blending each resin with starch, modified starch, skin powder, pulverized cellulose or the like.
Among the above-mentioned various resins, the polyolefin-based resins, the polycarbonates and the degradable resins are preferable, and the degradable resins are especially preferable in that the copolymer (A) and the resin (B) can more homogeneously be mixed without separation. Among the degradable resins, the aliphatic polyesters, the polyactides and the polylactones are preferable, the aliphatic polyesters are more preferable, and the polyhydroxycarboxylic acids are most preferable, from the viewpoint of compatibility with the copolymer (A).
In the present invention, the polyhydroxycarboxylic acid means a polymer or a copolymer of a hydroxycarboxylic acid having both of a hydroxyl group and a carboxyl group. As the hydroxycarboxylic acids, preferable are lactic acid, glycolic acid, hydroxycaproic acid, hydroxybutanoic acid, hydroxypropionic acid and the like. In the polyhydroxycarboxylic acid, a constitutional moiety (a copolymerized unit) other than the hydroxycarboxylic acid may be present. However, in the polyhydroxycarboxylic acid, a ratio of the constitutional unit derived from the hydroxycarboxylic acid is preferably 20 mol % or more, more preferably 50 mol % or more.
The polyhydroxycarboxylic acids which can most suitably be used include polylactic acid, lactic acid-glycolic acid copolymer and polycaprolactone.
In the present invention, the molecular weight of the resin (B) is not particularly limited. Nevertheless, in view of the easiness of mixing with the copolymer (A), the weight-average molecular weight of the resin (B) is preferably within the range of 1000 to 1000000, more preferably 3000 to 500000.
The copolymer (A) which can be used in the present invention is a block or a graft copolymer having a polyamino acid as a hydrophilic segment (a-1) and a degradable polymer as a hydrophobic segment (a-2).
In the present invention, xe2x80x9cthe hydrophobic segmentxe2x80x9d means a degradable polymer which is sparingly soluble or insoluble especially in water, or a segment derived from this polymer, and it is less hydrophilic than the hydrophilic segment. xe2x80x9cThe hydrophilic segmentxe2x80x9d means a polymer which is soluble in water or which is more hydrophilic than the hydrophobic segment even if it is sparingly soluble in water, or a segment derived from this polymer.
A preferable embodiment of the hydrophilic segment (a-1) of the copolymer (A) is constituted of a constitutional unit derived from aspartic acid, and a preferable embodiment of the hydrophobic segment (a-2) is constituted of a constitutional unit derived from the following hydroxycarboxylic acids, polylactides, polylactones or carbonates.
(1) Hydroxycarboxylic acids
xcex1-Hydroxymonocarboxylic acids (e.g., glycolic acid, lactic acid, 2-hydroxybutyric acid, 2-hydroxyvaleric acid, 2-hydroxycaproic acid and 2-hydroxycapric acid); hydroxydicarboxylic acids (e.g., malic acid); hydroxytricarboxylic acids (e.g., citric acid); and the like.
(2) Lactides
For example, glycolide, lactide, p-dioxanone, 1,4-benzylmalolactonate, malite benzyl ester, 3-[(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione and tetramethyl glycolide.
(3) Lactones
For example, xcex2-propiolactone, xcex2-butyrolactone, xcex1, xcex1-bischloromethylpropiolactone, xcex3-butyrolactone, xcex3-valerolactone, xcex4-valerolactone, 3-n-propyl-xcex4-valerolactone, 6,6-dimethyl-xcex4-valerolactone, 3,3,6-trimethyl-1,4-dioxan-dione, xcex5-caprolactone, dioxepanone, 4-methyl-7-isopropyl-xcex5-caprolactone and N-benzyloxycarbonyl-L-serin-xcex2-lactone.
(4) Carbonates
For example, ethylene carbonate, tetramethylene carbonate, trimethylene carbonate, neopentylene carbonate, ethylene oxolate and propylene oxolate.
Furthermore, acids containing one or more selected from the group consisting of the above hydroxycarboxylic acids as well as lactides and lactones derived from the hydroxycarboxylic acids are generally called hydroxycarboxylic acids. In addition, glycolic acid, lactic acid, 2-hydroxybutyric acid, 2-hydroxyvaleric acid, 2-hydroxycaproic acid and the like mentioned above are especially generally called xcex1-hydroxycarboxylic acids.
A preferable embodiment of the hydrophobic segment (a-2) of the copolymer (A) is a constitutional unit derived from a hydroxycarboxylic acid. Especially, it is preferable to use an xcex1-hydroxycarboxylic acid, glycolide, lactide, p-dioxanone, xcex2-propiolactone, xcex2-butyrolactone, xcex4-valerolactone or xcex5-caprolactone. Among them, more preferable is to use glycolic acid, lactic acid, glycolide, lactide or xcex5-caprolactone.
As the copolymer (A) of the present invention, an aspartic acid hydroxycarboxylic acid copolymer is preferable. This copolymer can be obtained by the copolymerization of aspartic acid with a hydroxycarboxylic acid or lactide, glycolide, p-dioxanone, xcex2-propiolactone, xcex2-butyrolactone, xcex4-valerolactone, xcex5-caprolactone or the like. In the structure of the aspartic acid-hydroxycarboxylic acid copolymer, there coexist at least a constitutional unit derived from aspartic acid and a constitutional unit derived from the hydroxycarboxylic acid. The copolymer preferably contains 1 mol % or more of the constitutional unit derived from aspartic acid and 1 mol % or more of the constitutional unit derived from the hydroxycarboxylic acid. Aspartic acid can dehydrate/condense to form a polymer having a succinimide unit, and so the constitutional unit derived from aspartic acid also may include such a succinimide unit.
The succinimide unit means the constitutional unit represented by the following formula (1): 
The composition ratio of the unit derived from aspartic acid to the unit derived from the hydroxycarboxylic acid in the aspartic acid-hydroxycarboxylic acid copolymer is preferably within a range of 1/1 to 1/50.
In order to form the constitutional unit derived from the hydroxycarboxylic acid in the aspartic acid-hydroxycarboxylic acid copolymer, it is preferable to use at least one selected from the group consisting of an xcex1-hydroxycarboxylic acid, glycolide, lactide, p-dioxanone, xcex2-propiolactone, xcex2-butyrolactone, xcex4-valerolactone and xcex5-caprolactone. It is more preferable to use at least one selected form the group consisting of glycolic acid, lactic acid, glycolide, lactide, p-dioxanone, 2-hydroxybutyric acid, 2-hydroxyvaleric acid, 2-hydroxycaproic acid, xcex2-propiolactone, xcex2-butyrolactone, xcex4-valerolactone and xcex5-caprolactone. It is particularly preferable to use at least one selected from the group consisting of clycolic acid, lactic acid, glycolide, lactide and xcex5-caprolactone. Most preferable is to use lactic acid.
The aspartic acid-hydroxycarboxylic acid copolymer may contain a constitutional unit other than aspartic acid and the hydroxycarboxylic acid as a result of the copolymerization. However, the amount of the other constitutional unit is required to be such a level as not to seriously impair the properties of the aspartic acid-hydroxycarboxylic acid copolymer. In view of this point, the amount of the other constitutional unit should be about 20 mol % or less.
A method for producing the aspartic acid-hydroxycarboxylic acid copolymer is not particularly limited. Usually, the copolymer can be obtained by mixing aspartic acid with the hydroxycarboxylic acid in a desired ratio, followed by dehydration/condensation with heating under a reduced pressure. Alternatively, it can also be obtained by reacting aspartic acid with a cyclic anhydride compound of a hydroxycarboxylic acid such as lactide (LTD), glycolide (GLD) or caprolactone (CL).
The preferable aspartic acid-hydroxycarboxylic acid copolymer in the present invention can be obtained by heating a mixture of aspartic acid and one or more compounds selected from the group consisting of lactide, glycolide, lactic acid and glycolic acid. The resultant copolymer is a copolymer having both of at least a succinimide unit and/or an aspartic acid unit, and a lactic acid unit and/or a glycolic acid unit as repeating units.
The resin composition of the present invention can be obtained by, for example, mixing the aspartic acid-hydroxycarboxylic acid copolymer having a weight-average molecular weight of 1000 to 100000 with the polyhydroxycarboxylic acid having a weight-average molecular weight of 3000 to 500000. A composition ratio of these materials is preferably 0.01 to 3300 parts by weight of the aspartic acid-hydroxycarboxylic acid copolymer to 100 parts by weight of the polyhydroxycarboxylic acid. When the composition ratio of the aspartic acid-hydroxycarboxylic acid copolymer is too high, a thermoplastic resin composition having a high degradation rate is obtained. When the composition ratio of the aspartic acid-hydroxycarboxylic acid copolymer to the polyhydroxycarboxylic acid is too low, it is difficult to expect an effect of accelerating the degradation rate of the polyhydroxycarboxylic acid and an effect of inhibiting the heat deterioration thereof.
When a composition that does not seriously impair the properties of the polyhydroxycarboxylic acid is desired, the composition ratio by weight of the aspartic acid-hydroxycarboxylic acid copolymer to the polyhydroxycarboxylic acid is preferably adjusted to a range of about 1/99 to 33/67.
As described above, mixing 1 to 50% by weight of the aspartic acid-hydroxycarboxylic acid copolymer with the resin (the polyhydroxycarboxylic acid or the like) permits the acceleration of the hydrolysis of the resin and the inhibition of the heat deterioration of the resin.
No particular restriction is put on a technique for mixing the aspartic acid-hydroxycarboxylic acid copolymer with the polyhydroxycarboxylic acid. Preferably, both the compounds are heated/melted, or they are dissolved in a solvent and then stirred/mixed.
Both the compounds are well compatible with each other owing to a hydroxycarboxylic acid segment present in the aspartic acid-hydrocarboxylic acid copolymer. For example, when 5 parts by weight of the aspartic acid-lactic acid copolymer having a copolymer composition ratio of aspartic acid to lactic acid of {fraction (1/5+L )} and a weight-average molecular weight of 20000 are added to 95 parts by weight of PLA having a weight-average molecular weight of about 150000 and they are then melted and mixed at 200xc2x0 C. by the use of a small-sized kneader, both the materials are well compatible with each other. The resultant mixture is then subjected to processing such as pressing to obtain a film having a transparency similar to that of a PLA film. The thus obtained film shows about the same mechanical strength properties (tensile strength, elongation, elasticity modulus, etc.) as that of the PLA film.
For instance, in the case of the PLA film having a weight-average molecular weight of about 150000, its mechanical strength properties and appearance scarcely change even after it is immersed in neutral water at 37xc2x0 C. for about 5 months. On the other hand, the film obtained from the resin composition of the present invention within the above-mentioned range whitens after about 1 month under the same conditions, and the strength of the film becomes 0 and the molecular weight thereof decreases to 20000 or less after about 5 months.
Furthermore, for example, when 5 parts by weight of polyaspartic acid or 5 parts by weight of polysuccinimide are added to 95 parts by weight of PLA and mixing is then tried by means of a kneader in the same manner as above, both the compounds are not compatible with each other, so that even after pressing, a non-homogeneous and opaque film having a low strength is merely obtained.
It is known that the polyhydroxycarboxylic acid is labile to heat and therefore its molecular weight is prone to decrease by heating during molding such as kneading or injection. Surprisingly, when the aspartic acid-hydroxycarboxylic acid copolymer is mixed with the polyhydroxycarboxylic acid, the heat deterioration can be inhibited.
Furthermore, for example, in the case that PLA having a weight-average molecular weight of 280000 is melted at 220xc2x0 C. in air, this molecular weight decreases to 140000, a weight loss of 5.6% after 1 hour, and to 60000 and 40000 after 2 hours and 3 hours, respectively. On the other hand, in the case that 5 parts by weight of the aspartic acid-lactic acid copolymer having a weight-average molecular weight of 20000 and a copolymer composition ratio of aspartic acid to lactic acid of {fraction (1/5+L )} are added to 95 parts by weight of PLA having the same weight-average molecular weight of 280000 and they are then mixed, even when the resultant mixture is heated/melted under the same conditions, the molecular weight and the weight loss of the PLA after 1 hour are 210000 and 0.4%, respectively. Even after 2 hours and 3 hours, the molecular weights are 180000 and 130000, respectively. Accordingly, the effect of suppressing the heat deterioration can be apparently confirmed.
The aspartic acid-hydroxycarboxylic acid copolymer is typically a polymer, having as aspartic acid unit and a lactic acid unit and/or a glycolic acid unit as repeating units, which can be obtained by ring-opening a succinimide unit by hydrolysis, this succinimide unit being a constitutional unit of a copolymer formed by heating a mixture of aspartic acid and lactide and/or glycolide. A carboxyl group at a molecular chain end of the polymer is not necessarily a COOH group, and at this chain end, there may be formed a salt of a base such as an alkaline metal, an alkaline earth metal or an amine.
With respect to a copolymer, having at least a succinimide unit and/or an aspartic acid unit as well as a lactic acid unit and/or a glycolic acid unit as repeating units, which can be obtained by heating a mixture of aspartic acid and at least one compound selected from the group consisting of lactide, glycolide, lactic acid and glycolic acid, the structure of this copolymer can be confirmed by a known analytical technique such as the measurement of a nuclear magnetic resonance (NMR) spectrum and the measurement of an infrared absorption (IR) spectrum. and the measurement of an infrared absorption (IR) spectrum.
The aspartic acid unit contained in the structure of the aspartic acid-hydroxycarboxylic acid copolymer may be a mixture of an xcex1-amide type monomer unit and a xcex2-amide type monomer unit, and a ratio of both the units is not particularly limited.
The molecular weight of the aspartic acid-hydroxycarboxylic acid copolymer is preferably in a range of about 1000 to 100000 in terms of weight-average molecular weight in view of good mixing with a polyhydroxycarboxylic acid as well as the increase of the degradation accelerating effect and the heat deterioration inhibiting effect.
In the present invention, it is considered that the reason for the degradation accelerating effect is that the wettability of the resin composition is enhanced by mixing the copolymer (A) with the resin (B). The enhancement of the wettability can be judged by determining contact angles to water drops on a film made of a resin composition containing the copolymer (A) and the resin (B), and a film made of the resin (B) alone. In this case, the resin film may be any of a cast film, a thermally pressed film, a stretched film and the like. When the contact angles are compared before and after the addition of the copolymer (A), and if a difference between the contact angles is 2xc2x0 or more, it can be judged that the wettability of the resin is enhanced. If the difference is 40xc2x0 or more, it can be judged that the wettability is very enhanced.
Next, the present invention will be described in detail in accordance with some examples. Incidentally, physical properties and the like shown in the examples were determined as follows.
[1] Weight-average molecular weight (Mw) and molecular weight distribution (Mw/Mn) of a polymer
A sample was dissolved in dimethylformamide (DMF) or chloroform (concentration=0.5% by weight), and a weight-average molecular weight (hereinafter referred to as xe2x80x9cMwxe2x80x9d) and a molecular weight distribution (hereinafter referred to as xe2x80x9cMw/Mnxe2x80x9d) of the polymer were determined by means of gel permeation chromatography (hereinafter referred to as xe2x80x9cGPCxe2x80x9d). As a reference, polystyrene was used.
[2] Infrared absorption (IR) spectrum
A polymer sample powder was sufficiently mixed with a KBr powder, and the resultant powder mixture was then pressed under degassing to form a pellet. A spectrum was measured by means of an ET-IR apparatus.
[3] Nuclear magnetic resonance spectrum (NMR spectrum)
A sample was dissolved in deuterated dimethyl sulfoxide (concentration=7% by weight), and H-NMR (400 MHz) and C-NMR (100 MHz) spectra were measured at room temperature by the use of a nuclear magnetic resonance apparatus.
[4] Tensile strength, tensile modulus of elasticity, elongation at breaking of a film
A film stamped out in a dumbbell shape was drawn at a tensile rate of 20 mm/min by the use of a tensile testing machine to measure stresses, thereby obtaining tensile strength at breaking, tensile modulus of elasticity, and elongation at breaking.
[5] Evaluation of mixing state of component A and component B
A mixing state of a component A and a component B in a formed film was judged in the following manner.
⊚: The components A and B were mixed homogeneously and transparently without separation.
◯: The components A and B were mixed homogeneously without separation.
xcex94: The components A and B were mixed without separation.